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http://dx.doi.org/10.4062/biomolther.2016.186

Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis  

Zhang, Xiaohan (Pharmacology Laboratory, College of Pharmacy, Chonnam National University)
Kim, Kyeong-Man (Pharmacology Laboratory, College of Pharmacy, Chonnam National University)
Publication Information
Biomolecules & Therapeutics / v.25, no.1, 2017 , pp. 26-43 More about this Journal
Abstract
Endocytosis is a process by which cells absorb extracellular materials via the inward budding of vesicles formed from the plasma membrane. Receptor-mediated endocytosis is a highly selective process where receptors with specific binding sites for extracellular molecules internalize via vesicles. G protein-coupled receptors (GPCRs) are the largest single family of plasma-membrane receptors with more than 1000 family members. But the molecular mechanisms involved in the regulation of GPCRs are believed to be highly conserved. For example, receptor phosphorylation in collaboration with ${\beta}$-arrestins plays major roles in desensitization and endocytosis of most GPCRs. Nevertheless, a number of subsequent studies showed that GPCR regulation, such as that by endocytosis, occurs through various pathways with a multitude of cellular components and processes. This review focused on i) functional interactions between homologous and heterologous pathways, ii) methodologies applied for determining receptor endocytosis, iii) experimental tools to determine specific endocytic routes, iv) roles of small guanosine triphosphate-binding proteins in GPCR endocytosis, and v) role of post-translational modification of the receptors in endocytosis.
Keywords
G protein-coupled receptor; Endocytosis; Ral; ARF6; Glycosylation; Palmitoylation;
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1 Adlanmerini, M., Solinhac, R., Abot, A., Fabre, A., Raymond-Letron, I., Guihot, A. L., Boudou, F., Sautier, L., Vessieres, E., Kim, S.H, Liere, P., Fontaine, C., Krust, A., Chambon, P., Katzenellenbogen, J. A., Gourdy, P., Shaul, P. W., Henrion, D., Arnal, J. F. and Lenfant, F. (2014) Mutation of the palmitoylation site of estrogen receptor ${\alpha}$ in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc. Natl. Acad. Sci. U.S.A. 111, E283-E290.   DOI
2 Alaluf, S., Mulvihill, E. R. and McIlhinney, R. A. (1995) Palmitoylation of metabotropic glutamate receptor subtype 4 but not 1 ${\alpha}$ expressed in permanently transfected BHK cells. Biochem. Soc. Trans. 23, 87S.   DOI
3 Alvarez, R., Lopez, D. J., Casas, J., Llado, V., Higuera, M., Nagy, T., Barcelo, M., Busquets, X. and Escriba, P. V. (2015) G protein-membrane interactions I: G${\alpha}$i1 myristoyl and palmitoyl modifications in protein-lipid interactions and its implications in membrane microdomain localization. Biochim. Biophys. Acta 1851, 1511-1520.   DOI
4 Anderson, R. G. (1998) The caveolae membrane system. Annu. Rev. Biochem. 67, 199-225.   DOI
5 Antonescu, C. N., Danuser, G. and Schmid, S. L. (2010) Phosphatidic acid plays a regulatory role in clathrin-mediated endocytosis. Mol. Biol. Cell 21, 2944-2952.   DOI
6 Booden, M. A., Eckert, L. B., Der, C. J. and Trejo, J. (2004) Persistent signaling by dysregulated thrombin receptor trafficking promotes breast carcinoma cell invasion. Mol. Cell. Biol. 24, 1990-1999.   DOI
7 Bos, J. L. (1998) All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral. EMBO J. 17, 6776-6782.   DOI
8 Nakashima, S., Morinaka, K., Koyama, S., Ikeda, M., Kishida, M., Okawa, K., Iwamatsu, A., Kishida, S. and Kikuchi, A. (1999) Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. EMBO J. 18, 3629-3642.   DOI
9 Nakatsu, F., Perera, R. M., Lucast, L., Zoncu, R., Domin, J., Gertler, F. B., Toomre, D. and De Camilli, P. (2010) The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics. J. Cell Biol. 190, 307-315.   DOI
10 Nelson, C. D., Perry, S. J., Regier, D. S., Prescott, S. M., Topham, M. K. and Lefkowitz, R. J. (2007) Targeting of diacylglycerol degradation to M1 muscarinic receptors by ${\beta}$-arrestins. Science 315, 663-666.   DOI
11 Novick, P. and Zerial, M. (1997) The diversity of Rab proteins in vesicle transport. Curr. Opin. Cell Biol. 9, 496-504.   DOI
12 Oddi, S., Dainese, E., Sandiford, S., Fezza, F., Lanuti, M., Chiurchiu, V., Totaro, A., Catanzaro, G., Barcaroli, D., De Laurenzi, V., Centonze, D., Mukhopadhyay, S., Selent, J., Howlett, A. C. and Maccarrone, M. (2012) Effects of palmitoylation of Cys(415) in helix 8 of the CB(1) cannabinoid receptor on membrane localization and signalling. Br. J. Pharmacol. 165, 2635-2651.   DOI
13 Macia, E., Luton, F., Partisani, M., Cherfils, J., Chardin, P. and Franco, M. (2004) The GDP-bound form of Arf6 is located at the plasma membrane. J. Cell Sci. 117, 2389-2398.   DOI
14 Posor, Y., Eichhorn-Grunig, M. and Haucke, V. (2015) Phosphoinositides in endocytosis. Biochim. Biophys. Acta 1851, 794-804.   DOI
15 Acconcia, F., Ascenzi, P., Bocedi, A., Spisni, E., Tomasi, V., Trentalance, A., Visca, P. and Marino, M. (2005) Palmitoylation-dependent estrogen receptor ${\alpha}$ membrane localization: regulation by $17{\beta}$-estradiol. Mol. Biol. Cell 16, 231-237.   DOI
16 Adachi, N., Hess, D. T., McLaughlin, P. and Stamler, J. S. (2016) S-palmitoylation of a novel site in the ${\beta}2$-adrenergic receptor associated with a novel intracellular itinerary. J. Biol. Chem. 291, 20232-20246.   DOI
17 Adams, M. N., Christensen, M. E., He, Y., Waterhouse, N. J. and Hooper, J. D. (2011) The role of palmitoylation in signalling, cellular trafficking and plasma membrane localization of protease-activated receptor-2. PLoS ONE 6, e28018.   DOI
18 Luttrell, L. M., Roudabush, F. L., Choy, E. W., Miller, W. E., Field, M. E., Pierce, K. L. and Lefkowitz, R. J. (2001) Activation and targeting of extracellular signal-regulated kinases by ${\beta}$-arrestin scaffolds. Proc. Natl. Acad. Sci. U.S.A. 98, 2449-2454.   DOI
19 Marchese, A., Chen, C., Kim, Y. M. and Benovic, J. L. (2003) The ins and outs of G protein-coupled receptor trafficking. Trends Biochem. Sci. 28, 369-376.   DOI
20 Marotti, L. A., Jr., Newitt, R., Wang, Y., Aebersold, R. and Dohlman, H. G. (2002) Direct identification of a G protein ubiquitination site by mass spectrometry. Biochemistry 41, 5067-5074.   DOI
21 Menard, L., Ferguson, S. S., Barak, L. S., Bertrand, L., Premont, R. T., Colapietro, A. M., Lefkowitz, R. J. and Caron, M. G. (1996) Members of the G protein-coupled receptor kinase family that phosphorylate the ${\beta}2$-adrenergic receptor facilitate sequestration. Biochemistry 35, 4155-4160.   DOI
22 Arriza, J. L., Dawson, T. M., Simerly, R. B., Martin, L. J., Caron, M. G., Snyder, S. H. and Lefkowitz, R. J. (1992) The G-protein-coupled receptor kinases ${\beta}$ ARK1 and ${\beta}$ ARK2 are widely distributed at synapses in rat brain. J. Neurosci. 12, 4045-4055.   DOI
23 Attramadal, H., Arriza, J. L., Aoki, C., Dawson, T. M., Codina, J., Kwatra, M. M., Snyder, S. H., Caron, M. G. and Lefkowitz, R. J. (1992) ${\beta}$-arrestin2, a novel member of the arrestin/${\beta}$-arrestin gene family. J. Biol. Chem. 267, 17882-17890.
24 Meitzen, J., Luoma, J. I., Boulware, M. I., Hedges, V. L., Peterson, B. M., Tuomela, K., Britson, K. A. and Mermelstein, P. G. (2013) Palmitoylation of estrogen receptors is essential for neuronal membrane signaling. Endocrinology 154, 4293-4304.   DOI
25 Min, C., Zheng, M., Zhang, X., Caron, M. G. and Kim, K. M. (2013) Novel roles for ${\beta}$-arrestins in the regulation of pharmacological sequestration to predict agonist-induced desensitization of dopamine D3 receptors. Br. J. Pharmacol. 170, 1112-1129.   DOI
26 Min, C., Zheng, M., Zhang, X., Guo, S., Kwon, K. J., Shin, C. Y., Kim, H. S., Cheon, S. H. and Kim, K. M. (2015) N-linked Glycosylation on the N-terminus of the dopamine $D_2$ and D3 receptors determines receptor association with specific microdomains in the plasma membrane. Biochim. Biophys. Acta 1853, 41-51.   DOI
27 Krasel, C., Dammeier, S., Winstel, R., Brockmann, J., Mischak, H. and Lohse, M. J. (2001) Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. J. Biol. Chem. 276, 1911-1915.   DOI
28 O'Dowd, B. F., Hnatowich, M., Caron, M. G., Lefkowitz, R. J. and Bouvier, M. (1989) Palmitoylation of the human ${\beta}2$-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J. Biol. Chem. 264, 7564-7569.
29 O'Hayre, M., Degese, M. S. and Gutkind, J. S. (2014) Novel insights into G protein and G protein-coupled receptor signaling in cancer. Curr. Opin. Cell Biol. 27, 126-135.   DOI
30 Kawate, N. and Menon, K. M. (1994) Palmitoylation of luteinizing hormone/human choriogonadotropin receptors in transfected cells. Abolition of palmitoylation by mutation of Cys-621 and Cys-622 residues in the cytoplasmic tail increases ligand-induced internalization of the receptor. J. Biol. Chem. 269, 30651-30658.
31 Krauss, M., Kinuta, M., Wenk, M. R., De Camilli, P., Takei, K. and Haucke, V. (2003) ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type $I{\gamma}$. J. Cell Biol. 162, 113-124.
32 McLauchlan, H., Newell, J., Morrice, N., Osborne, A., West, M. and Smythe, E. (1998) A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits. Curr. Biol. 8, 34-45.   DOI
33 Matsuzaki, T., Hanai, S., Kishi, H., Liu, Z., Bao, Y., Kikuchi, A., Tsuchida, K. and Sugino, H. (2002) Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway. J. Biol. Chem. 277, 19008-19018.   DOI
34 McCaffrey, P. G., Friedman, B. and Rosner, M. R. (1984) Diacylglycerol modulates binding and phosphorylation of the epidermal growth factor receptor. J. Biol. Chem. 259, 12502-12507.
35 McDonald, P. H., Chow, C. W., Miller, W. E., Laporte, S. A., Field, M. E., Lin, F. T., Davis, R. J. and Lefkowitz, R. J. (2000) ${\beta}$-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290, 1574-1577.   DOI
36 Houndolo, T., Boulay, P. L. and Claing, A. (2005) G protein-coupled receptor endocytosis in ADP-ribosylation factor 6-depleted cells. J. Biol. Chem. 280, 5598-5604.   DOI
37 Mishra, S. and Murphy, L. J. (2004) Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 as an insulin-like growth factor-binding protein-3 kinase. J. Biol. Chem. 279, 23863-23868.   DOI
38 Mitchell, R., Robertson, D. N., Holland, P. J., Collins, D., Lutz, E. M. and Johnson, M. S. (2003) ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor. J. Biol. Chem. 278, 33818-33830.   DOI
39 Moffett, S., Adam, L., Bonin, H., Loisel, T. P., Bouvier, M. and Mouillac, B. (1996) Palmitoylated cysteine 341 modulates phosphorylation of the ${\beta}2$-adrenergic receptor by the cAMP-dependent protein kinase. J. Biol. Chem. 271, 21490-21497.   DOI
40 Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A. J., Frohman, M. A. and Kanaho, Y. (1999) Phosphatidylinositol 4-phosphate 5-kinase ${\alpha}$ is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99, 521-532.   DOI
41 Huang, C. and Tai, H. H. (1998) Prostaglandin E2 receptor $EP3{\alpha}$ subtype: the role of N-glycosylation in ligand binding as revealed by site-directed mutagenesis. Prostaglandins Leukot. Essent. Fatty Acids 59, 265-271.   DOI
42 Huang, J., Mahavadi, S., Sriwai, W., Grider, J. R. and Murthy, K. S. (2007) Cross-regulation of VPAC(2) receptor desensitization by M(3) receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G867-G874.   DOI
43 Hukovic, N., Panetta, R., Kumar, U., Rocheville, M. and Patel, Y. C. (1998) The cytoplasmic tail of the human somatostatin receptor type 5 is crucial for interaction with adenylyl cyclase and in mediating desensitization and internalization. J. Biol. Chem. 273, 21416-21422.   DOI
44 Kim, J., Ahn, S., Ren, X. R., Whalen, E. J., Reiter, E., Wei, H. and Lefkowitz, R. J. (2005) Functional antagonism of different G protein-coupled receptor kinases for ${\beta}$-arrestin-mediated angiotensin II receptor signaling. Proc. Natl. Acad. Sci. U.S.A. 102, 1442-1447.   DOI
45 Kelly, B. T., Graham, S. C., Liska, N., Dannhauser, P. N., Honing, S., Ungewickell, E. J. and Owen, D. J. (2014) Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated switch. Science 345, 459-463.   DOI
46 Kelly, E., Bailey, C. P. and Henderson, G. (2008) Agonist-selective mechanisms of GPCR desensitization. Br. J. Pharmacol. 153 Suppl 1, S379-S388.
47 Kennedy, M. E. and Limbird, L. E. (1993) Mutations of the ${\alpha}2A$-adrenergic receptor that eliminate detectable palmitoylation do not perturb receptor-G-protein coupling. J. Biol. Chem. 268, 8003-8011.
48 Kim, J. H., Cho, E. Y., Min, C., Park, J. H. and Kim, K. M. (2008) Characterization of functional roles of DRY motif in the 2nd intracellular loop of dopamine D2 and D3 receptors. Arch. Pharm. Res. 31, 474-481.   DOI
49 Kim, J. H., Lee, S. D., Han, J. M., Lee, T. G., Kim, Y., Park, J. B., Lambeth, J. D., Suh, P. G. and Ryu, S. H. (1998) Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA. FEBS Lett. 430, 231-235.   DOI
50 Zhang, X., Le, H. T., Zhang, X., Zheng, M., Choi, B. G. and Kim, K. M. (2016b) Palmitoylation on the carboxyl terminus tail is required for the selective regulation of dopamine $D_2$ versus D3 receptors. Biochim. Biophys. Acta 1858, 2152-2162.   DOI
51 Zhang, X., Sun, N., Zheng, M. and Kim, K. M. (2016c) Clathrin-mediated endocytosis is responsible for the lysosomal degradation of dopamine D3 receptor. Biochem. Biophys. Res. Commun. 476, 245-251.   DOI
52 Lawrence, J., Mundell, S. J., Yun, H., Kelly, E. and Venkateswarlu, K. (2005) Centaurin-${\alpha}_1$, an ADP-ribosylation factor 6 GTPase activating protein, inhibits ${\beta}_2$-adrenoceptor internalization. Mol. Pharmacol. 67, 1822-1828.   DOI
53 Lahaie, N., Kralikova, M., Prezeau, L., Blahos, J. and Bouvier, M. (2016) Post-endocytotic deubiquitination and degradation of the metabotropic ${\gamma}$-aminobutyric acid receptor by the ubiquitin-specific protease 14. J. Biol. Chem. 291, 7156-7170.   DOI
54 Lajoie, P. and Nabi, I. R. (2010) Lipid rafts, caveolae, and their endocytosis. Int. Rev. Cell Mol. Biol. 282, 135-163.
55 Laporte, S. A., Oakley, R. H., Zhang, J., Holt, J. A., Ferguson, S. S., Caron, M. G. and Barak, L. S. (1999) The ${\beta}2$-adrenergic receptor/${\beta}$arrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc. Natl. Acad. Sci. U.S.A. 96, 3712-3717.   DOI
56 Lefkowitz, R. J., Pierce, K. L. and Luttrell, L. M. (2002) Dancing with different partners: protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G protein-coupling specificity. Mol. Pharmacol. 62, 971-974.   DOI
57 Hutagalung, A. H. and Novick, P. J. (2011) Role of Rab GTPases in membrane traffic and cell physiology. Physiol. Rev. 91, 119-149.   DOI
58 Filipek, S., Stenkamp, R. E., Teller, D. C. and Palczewski, K. (2003) G protein-coupled receptor rhodopsin: a prospectus. Annu. Rev. Physiol. 65, 851-879.   DOI
59 Fukata, M., Fukata, Y., Adesnik, H., Nicoll, R. A. and Bredt, D. S. (2004) Identification of PSD-95 palmitoylating enzymes. Neuron 44, 987-996.   DOI
60 Funakoshi, Y., Hasegawa, H. and Kanaho, Y. (2011) Regulation of PIP5K activity by Arf6 and its physiological significance. J. Cell. Physiol. 226, 888-895.   DOI
61 Iiri, T., Backlund, P. S., Jr., Jones, T. L., Wedegaertner, P. B. and Bourne, H. R. (1996) Reciprocal regulation of $G_s{\alpha}$ by palmitate and the ${\beta}{\gamma}$ subunit. Proc. Natl. Acad. Sci. U.S.A. 93, 14592-14597.   DOI
62 Ulloa-Aguirre, A., Timossi, C., Damian-Matsumura, P. and Dias, J. A. (1999) Role of glycosylation in function of follicle-stimulating hormone. Endocrine 11, 205-215.   DOI
63 van Dam, E. M. and Robinson, P. J. (2006) Ral: mediator of membrane trafficking. Int. J. Biochem. Cell Biol. 38, 1841-1847.   DOI
64 van der Bliek, A. M., Redelmeier, T. E., Damke, H., Tisdale, E. J., Meyerowitz, E. M. and Schmid, S. L. (1993) Mutations in human dynamin block an intermediate stage in coated vesicle formation. J. Cell Biol. 122, 553-563.   DOI
65 Vickery, R. G. and von Zastrow, M. (1999) Distinct dynamin-dependent and -independent mechanisms target structurally homologous dopamine receptors to different endocytic membranes. J. Cell Biol. 144, 31-43.   DOI
66 Vieira, A. V., Lamaze, C. and Schmid, S. L. (1996) Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274, 2086-2089.   DOI
67 von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M. J., MacGregor, K. A., Tomilin, N., Pechstein, A., Chau, N., Chircop, M., Sakoff, J., von Kries, J. P., Saenger, W., Krausslich, H. G., Shupliakov, O., Robinson, P. J., McCluskey, A. and Haucke, V. (2011) Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146, 471-484.   DOI
68 Zheng, H., Chu, J., Qiu, Y., Loh, H. H. and Law, P. Y. (2008) Agonistselective signaling is determined by the receptor location within the membrane domains. Proc. Natl. Acad. Sci. U.S.A. 105, 9421-9426.   DOI
69 Zhang, X. and Kim, K. M. (2016) Palmitoylation of the carboxyl-terminal tail of dopamine D4 receptor is required for surface expression, endocytosis, and signaling. Biochem. Biophys. Res. Commun. 479, 398-403.   DOI
70 Zhang, Z., Austin, S. C. and Smyth, E. M. (2001) Glycosylation of the human prostacyclin receptor: role in ligand binding and signal transduction. Mol. Pharmacol. 60, 480-487.
71 Zheng, H., Loh, H. H. and Law, P. Y. (2013) Posttranslation modification of G protein-coupled receptor in relationship to biased agonism. Meth. Enzymol. 522, 391-408.
72 Zheng, H., Pearsall, E. A., Hurst, D. P., Zhang, Y., Chu, J., Zhou, Y., Reggio, P. H., Loh, H. H. and Law, P. Y. (2012) Palmitoylation and membrane cholesterol stabilize mu-opioid receptor homodimerization and G protein coupling. BMC Cell Biol. 13, 6.   DOI
73 Zheng, M., Zhang, X., Guo, S., Zhang, X., Choi, H. J., Lee, M. Y. and Kim, K. M. (2015) $PKC{\beta}II$ inhibits the ubiquitination of ${\beta}$-arrestin2 in an autophosphorylation-dependent manner. FEBS Lett. 589, 3929-3937.   DOI
74 Godi, A., Pertile, P., Meyers, R., Marra, P., Di Tullio, G., Iurisci, C., Luini, A., Corda, D. and De Matteis, M. A. (1999) ARF mediates recruitment of PtdIns-4-OH kinase-${\beta}$ and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat. Cell Biol. 1, 280-287.   DOI
75 Gao, Z., Ni, Y., Szabo, G. and Linden, J. (1999) Palmitoylation of the recombinant human A1 adenosine receptor: enhanced proteolysis of palmitoylation-deficient mutant receptors. Biochem. J. 342, 387-895.   DOI
76 Gilman, A. G. (1987) G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56, 615-649.   DOI
77 Glickman, M. H. and Ciechanover, A. (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373-428.   DOI
78 Goodman, O. B., Jr., Krupnick, J. G., Santini, F., Gurevich, V. V., Penn, R. B., Gagnon, A. W., Keen, J. H. and Benovic, J. L. (1996) ${\beta}$-arrestin acts as a clathrin adaptor in endocytosis of the ${\beta}2$-adrenergic receptor. Nature 383, 447-450.   DOI
79 Greaves, J. and Chamberlain, L. H. (2011) DHHC palmitoyl transferases: substrate interactions and (patho) physiology. Trends Biochem. Sci. 36, 245-253.   DOI
80 Shenoy, S. K., McDonald, P. H., Kohout, T. A. and Lefkowitz, R. J. (2001) Regulation of receptor fate by ubiquitination of activated ${\beta}2$-adrenergic receptor and ${\beta}$-arrestin. Science 294, 1307-1313.   DOI
81 Sibley, D. R., Benovic, J. L., Caron, M. G. and Lefkowitz, R. J. (1987) Regulation of transmembrane signaling by receptor phosphorylation. Cell 48, 913-922.   DOI
82 Dang, V. C. and Christie, M. J. (2012) Mechanisms of rapid opioid receptor desensitization, resensitization and tolerance in brain neurons. Br. J. Pharmacol. 165, 1704-1716.   DOI
83 von Zastrow, M. (2001) Role of endocytosis in signalling and regulation of G-protein-coupled receptors. Biochem. Soc. Trans. 29, 500-504.   DOI
84 Wedegaertner, P. B., Chu, D. H., Wilson, P. T., Levis, M. J. and Bourne, H. R. (1993) Palmitoylation is required for signaling functions and membrane attachment of $Gq{\alpha}$ and $Gs{\alpha}$. J. Biol. Chem. 268, 25001-25008.
85 Connor, M., Osborne, P. B. and Christie, M. J. (2004) Mu-opioid receptor desensitization: is morphine different? Br. J. Pharmacol. 143, 685-696.   DOI
86 Cosson, P., de Curtis, I., Pouyssegur, J., Griffiths, G. and Davoust, J. (1989) Low cytoplasmic pH inhibits endocytosis and transport from the trans-Golgi network to the cell surface. J. Cell Biol. 108, 377-387.   DOI
87 Czech, M. P. (2000) PIP2 and PIP3: complex roles at the cell surface. Cell 100, 603-606.   DOI
88 Davies, P. J., Davies, D. R., Levitzki, A., Maxfield, F. R., Milhaud, P., Willingham, M. C. and Pastan, I. H. (1980) Transglutaminase is essential in receptor-mediated endocytosis of ${\alpha}2$-macroglobulin and polypeptide hormones. Nature 283, 162-167.   DOI
89 DeFea, K. A., Zalevsky, J., Thoma, M. S., Dery, O., Mullins, R. D. and Bunnett, N. W. (2000) ${\beta}$-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J. Cell Biol. 148, 1267-1281.   DOI
90 Sibley, D. R. and Lefkowitz, R. J. (1985) Molecular mechanisms of receptor desensitization using the ${\beta}$-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 317, 124-129.   DOI
91 Sikarwar, A. S., Hinton, M., Santhosh, K. T., Chelikani, P. and Dakshinamurti, S. (2014) Palmitoylation of $G{\alpha}q$ determines its association with the thromboxane receptor in hypoxic pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 50, 135-143.
92 Soto, A. G. and Trejo, J. (2010) N-linked glycosylation of protease-activated receptor-1 second extracellular loop: a critical determinant for ligand-induced receptor activation and internalization. J. Biol. Chem. 285, 18781-18793.   DOI
93 Stadel, J. M., Nambi, P., Shorr, R. G., Sawyer, D. F., Caron, M. G. and Lefkowitz, R. J. (1983) Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the ${\beta}$-adrenergic receptor. Proc. Natl. Acad. Sci. U.S.A. 80, 3173-3177.   DOI
94 Stenmark, H., Parton, R. G., Steele-Mortimer, O., Lutcke, A., Gruenberg, J. and Zerial, M. (1994) Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J. 13, 1287-1296.
95 Budd, D. C., Rae, A. and Tobin, A. B. (1999) Activation of the mitogenactivated protein kinase pathway by a Gq/11-coupled muscarinic receptor is independent of receptor internalization. J. Biol. Chem. 274, 12355-12360.   DOI
96 Boulware, M. I., Weick, J. P., Becklund, B. R., Kuo, S. P., Groth, R. D. and Mermelstein, P. G. (2005) Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J. Neurosci. 25, 5066-5078.   DOI
97 Bremnes, T., Paasche, J. D., Mehlum, A., Sandberg, C., Bremnes, B. and Attramadal, H. (2000) Regulation and intracellular trafficking pathways of the endothelin receptors. J. Biol. Chem. 275, 17596-1604.   DOI
98 Bucci, C., Parton, R. G., Mather, I. H., Stunnenberg, H., Simons, K., Hoflack, B. and Zerial, M. (1992) The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70, 715-728.   DOI
99 Doherty, G. J. and McMahon, H. T. (2009) Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857-902.   DOI
100 DeGraff, J. L., Gagnon, A. W., Benovic, J. L. and Orsini, M. J. (1999) Role of arrestins in endocytosis and signaling of ${\alpha}2$-adrenergic receptor subtypes. J. Biol. Chem. 274, 11253-11259.   DOI
101 Donaldson, J. G., Cassel, D., Kahn, R. A. and Klausner, R. D. (1992) ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein ${\beta}$-COP to Golgi membranes. Proc. Natl. Acad. Sci. U.S.A. 89, 6408-6412.   DOI
102 Qanbar, R. and Bouvier, M. (2003) Role of palmitoylation/depalmitoylation reactions in G-protein-coupled receptor function. Pharmacol. Ther. 97, 1-33.   DOI
103 Rands, E., Candelore, M. R., Cheung, A. H., Hill, W. S., Strader, C. D. and Dixon, R. A. (1990) Mutational analysis of ${\beta}$-adrenergic receptor glycosylation. J. Biol. Chem. 265, 10759-10764.
104 Rankovic, M., Jacob, L., Rankovic, V., Brandenburg, L. O., Schroder, H., Hollt, V. and Koch, T. (2009) ADP-ribosylation factor 6 regulates mu-opioid receptor trafficking and signaling via activation of phospholipase $D_2$. Cell Signal. 21, 1784-1793.   DOI
105 Rastogi, R., Verma, J. K., Kapoor, A., Langsley, G. and Mukhopadhyay, A. (2016) Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania. J. Biol. Chem. 291, 14732-14746.   DOI
106 Rodal, S. K., Skretting, G., Garred, O., Vilhardt, F., van Deurs, B. and Sandvig, K. (1999) Extraction of cholesterol with methyl-${\beta}$-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol. Biol. Cell 10, 961-974.   DOI
107 Burgoyne, R. D. (1989) Small GTP-binding proteins. Trends Biochem. Sci. 14, 394-396.   DOI
108 Aziziyeh, A. I., Li, T. T., Pape, C., Pampillo, M., Chidiac, P., Possmayer, F., Babwah, A. V. and Bhattacharya, M. (2009) Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell. Signal. 21, 1207-1217.   DOI
109 Barak, L. S., Tiberi, M., Freedman, N. J., Kwatra, M. M., Lefkowitz, R. J. and Caron, M. G. (1994) A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated ${\beta}2$-adrenergic receptor sequestration. J. Biol. Chem. 269, 2790-2795.
110 Benovic, J. L., DeBlasi, A., Stone, W. C., Caron, M. G. and Lefkowitz, R. J. (1989) ${\beta}$-adrenergic receptor kinase: primary structure delineates a multigene family. Science 246, 235-240.   DOI
111 Cavenagh, M. M., Whitney, J. A., Carroll, K., Zhang, C. J., Boman, A. L., Rosenwald, A. G., Mellman, I. and Kahn, R. A. (1996) Intracellular distribution of Arf proteins in mammalian cells. Arf6 is uniquely localized to the plasma membrane. J. Biol. Chem. 271, 21767-21774.   DOI
112 Chardin, P. and Tavitian, A. (1986) The ral gene: a new ras related gene isolated by the use of a synthetic probe. EMBO J. 5, 2203-2208.
113 Chen, C. A. and Manning, D. R. (2000) Regulation of $g{\alpha}$ i palmitoylation by activation of the 5-hydroxytryptamine-1A receptor. J. Biol. Chem. 275, 23516-23522.   DOI
114 Cho, D., Zheng, M., Min, C., Ma, L., Kurose, H., Park, J. H. and Kim, K. M. (2010) Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine $D_2$ receptors. Mol. Endocrinol. 24, 574-586.   DOI
115 Okamoto, Y., Ninomiya, H., Tanioka, M., Sakamoto, A., Miwa, S. and Masaki, T. (1997) Palmitoylation of human endothelinB. Its critical role in G protein coupling and a differential requirement for the cytoplasmic tail by G protein subtypes. J. Biol. Chem. 272, 21589-21596.   DOI
116 Olkkonen, V. M. and Stenmark, H. (1997) Role of Rab GTPases in membrane traffic. Int. Rev. Cytol. 176, 1-85.
117 Ong, S. T., Freeley, M., Skubis-Zegadlo, J., Fazil, M. H., Kelleher, D., Fresser, F., Baier, G., Verma, N. K. and Long, A. (2014) Phosphorylation of Rab5a protein by protein kinase C is crucial for T-cell migration. J. Biol. Chem. 289, 19420-19434.   DOI
118 Ooi, C. E., Dell'Angelica, E. C. and Bonifacino, J. S. (1998) ADP-Ribosylation factor 1 (ARF1) regulates recruitment of the AP-3 adaptor complex to membranes. J. Cell Biol. 142, 391-402.   DOI
119 Romer, W., Pontani, L. L., Sorre, B., Rentero, C., Berland, L., Chambon, V., Lamaze, C., Bassereau, P., Sykes, C., Gaus, K. and Johannes, L. (2010) Actin dynamics drive membrane reorganization and scission in clathrin-independent endocytosis. Cell 140, 540-553.   DOI
120 Rohrer, J., Benedetti, H., Zanolari, B. and Riezman, H. (1993) Identification of a novel sequence mediating regulated endocytosis of the G protein-coupled ${\alpha}$-pheromone receptor in yeast. Mol. Biol. Cell 4, 511-521.   DOI
121 Rosenthal, W., Antaramian, A., Gilbert, S. and Birnbaumer, M. (1993) Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase. J. Biol. Chem. 268, 13030-13033.
122 Moffett, S., Mouillac, B., Bonin, H. and Bouvier, M. (1993) Altered phosphorylation and desensitization patterns of a human ${\beta}2$-adrenergic receptor lacking the palmitoylated Cys341. EMBO J. 12, 349-356.
123 Benovic, J. L., Kuhn, H., Weyand, I., Codina, J., Caron, M. G. and Lefkowitz, R. J. (1987) Functional desensitization of the isolated ${\beta}$-adrenergic receptor by the ${\beta}$-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc. Natl. Acad. Sci. U.S.A. 84, 8879-8882.   DOI
124 Benovic, J. L., Pike, L. J., Cerione, R. A., Staniszewski, C., Yoshimasa, T., Codina, J., Caron, M. G. and Lefkowitz, R. J. (1985) Phosphorylation of the mammalian ${\beta}$-adrenergic receptor by cyclic AMP-dependent protein kinase. Regulation of the rate of receptor phosphorylation and dephosphorylation by agonist occupancy and effects on coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. J. Biol. Chem. 260, 7094-7101.
125 Benovic, J. L., Strasser, R. H., Caron, M. G. and Lefkowitz, R. J. (1986) ${\beta}$-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc. Natl. Acad. Sci. U.S.A. 83, 2797-2801.   DOI
126 Moller, L. B., Pollanen, J., Ronne, E., Pedersen, N. and Blasi, F. (1993) N-linked glycosylation of the ligand-binding domain of the human urokinase receptor contributes to the affinity for its ligand. J. Biol. Chem. 268, 11152-11159.
127 Moore, C. A., Milano, S. K. and Benovic, J. L. (2007) Regulation of receptor trafficking by GRKs and arrestins. Annu. Rev. Physiol. 69, 451-482.   DOI
128 Parenti, M., Vigano, M. A., Newman, C. M., Milligan, G. and Magee, A. I. (1993) A novel N-terminal motif for palmitoylation of G-protein ${\alpha}$ subunits. Biochem. J. 291, 349-353.   DOI
129 Orcl, L., Palmer, D. J., Amherdt, M. and Rothman, J. E. (1993) Coated vesicle assembly in the Golgi requires only coatomer and ARF proteins from the cytosol. Nature 364, 732-734.   DOI
130 Palacios, F., Schweitzer, J. K., Boshans, R. L. and D'Souza-Schorey, C. (2002) ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat. Cell Biol. 4, 929-936.   DOI
131 Parton, R. G. and Simons, K. (2007) The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 8, 185-194.   DOI
132 Pearse, B. M. (1976) Clathrin: a unique protein associated with intracellular transfer of membrane by coated vesicles. Proc. Natl. Acad. Sci. U.S.A. 73, 1255-1259.   DOI
133 Mukherjee, S., Ghosh, R. N. and Maxfield, F. R. (1997) Endocytosis. Physiol. Rev. 77, 759-803.   DOI
134 Moss, J. and Vaughan, M. (1995) Structure and function of ARF proteins: activators of cholera toxin and critical components of intracellular vesicular transport processes. J. Biol. Chem. 270, 12327-12330.   DOI
135 Mostafapour, S., Kobilka, B. K. and von Zastrow, M. (1996) Pharmacological sequestration of a chimeric ${\beta}3$/${\beta}2$ adrenergic receptor occurs without a corresponding amount of receptor internalization. Recept. Signal Transduct. 6, 151-163.
136 Mott, H. R. and Owen, D. (2014) Structure and function of RLIP76 (RalBP1): an intersection point between Ras and Rho signalling. Biochem. Soc. Trans. 42, 52-58.   DOI
137 Mumby, S. M., Kleuss, C. and Gilman, A. G. (1994) Receptor regulation of G-protein palmitoylation. Proc. Natl. Acad. Sci. U.S.A. 91, 2800-2804.   DOI
138 Nabi, I. R. and Le, P. U. (2003) Caveolae/raft-dependent endocytosis. J. Cell Biol. 161, 673-677.   DOI
139 Ivanov, A. I. (2008) Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods Mol. Biol. 440, 15-33.
140 Itokawa, M., Toru, M., Ito, K., Tsuga, H., Kameyama, K., Haga, T., Arinami, T. and Hamaguchi, H. (1996) Sequestration of the short and long isoforms of dopamine $D_2$ receptors expressed in Chinese hamster ovary cells. Mol. Pharmacol. 49, 560-566.
141 Jacob, C., Cottrell, G. S., Gehringer, D., Schmidlin, F., Grady, E. F. and Bunnett, N. W. (2005) c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. J. Biol. Chem. 280, 16076-16087.   DOI
142 Jenkins, G. H., Fisette, P. L. and Anderson, R. A. (1994) Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically stimulated by phosphatidic acid. J. Biol. Chem. 269, 11547-11554.
143 Loerke, D., Mettlen, M., Yarar, D., Jaqaman, K., Jaqaman, H., Danuser, G. and Schmid, S. L. (2009) Cargo and dynamin regulate clathrin-coated pit maturation. PLoS Biol. 7, e57.
144 Lichnerova, K., Kaniakova, M., Park, S. P., Skrenkova, K., Wang, Y. X., Petralia, R. S., Suh, Y. H. and Horak, M. (2015) Two N-glycosylation sites in the GluN1 subunit are essential for releasing N-methyl-d-aspartate (NMDA) receptors from the endoplasmic reticulum. J. Biol. Chem. 290, 18379-18390.   DOI
145 Linder, M. E., Middleton, P., Hepler, J. R., Taussig, R., Gilman, A. G. and Mumby, S. M. (1993) Lipid modifications of G proteins: ${\alpha}$ subunits are palmitoylated. Proc. Natl. Acad. Sci. U.S.A. 90, 3675-3679.   DOI
146 Liu, R., Wang, D., Shi, Q., Fu, Q., Hizon, S. and Xiang, Y. K. (2012) Palmitoylation regulates intracellular trafficking of ${\beta}2$ adrenergic receptor/arrestin/phosphodiesterase 4D complexes in cardiomyocytes. PLoS ONE 7, e42658.   DOI
147 Lohse, M. J., Benovic, J. L., Codina, J., Caron, M. G. and Lefkowitz, R. J. (1990) ${\beta}$-Arrestin: a protein that regulates ${\beta}$-adrenergic receptor function. Science 248, 1547-1550.   DOI
148 Lorenz, K., Lohse, M. J. and Quitterer, U. (2003) Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426, 574-579.   DOI
149 Luo, J. Q., Liu, X., Frankel, P., Rotunda, T., Ramos, M., Flom, J., Jiang, H., Feig, L. A., Morris, A. J., Kahn, R. A. and Foster, D. A. (1998) Functional association between Arf and RalA in active phospholipase D complex. Proc. Natl. Acad. Sci. U.S.A. 95, 3632-3637.   DOI
150 Ji, S., Liu, X., Li, S., Shen, L., Li, F., Wang, J., Han, J. and Yao, L. (2003) PH domain of G protein-coupled receptor kinase-2 binds to protein kinase C (PKC) and negatively regulates activity of PKC kinase. Front. Biosci. 8, a34-a39.   DOI
151 Jiang, H., Luo, J. Q., Urano, T., Frankel, P., Lu, Z., Foster, D. A. and Feig, L. A. (1995) Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Nature 378, 409-412.   DOI
152 Jimenez-baranda, S., Gomez-Mouton, C., Rojas, A., Martinez-Prats, L., Mira, E., Ana Lacalle, R., Valencia, A., Dimitrov, D. S., Viola, A., Delgado, R., Martinez-A, C. and Manes, S. (2007) Filamin-A regulates actin-dependent clustering of HIV receptors. Nat. Cell Biol. 9, 838-846.   DOI
153 Jullien-Flores, V., Mahe, Y., Mirey, G., Leprince, C., Meunier-Bisceuil, B., Sorkin, A. and Camonis, J. H. (2000) RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J. Cell Sci. 113, 2837-2844.
154 Weir, D. L., Laing, E. D., Smith, I. L., Wang, L. F. and Broder, C. C. (2014) Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5. Virol. J. 11, 40.   DOI
155 Wenk, M. R., Pellegrini, L., Klenchin, V. A., Di Paolo, G., Chang, S., Daniell, L., Arioka, M., Martin, T. F. and De Camilli, P. (2001) PIP kinase $I{\gamma}$ is the major PI(4,5)P(2) synthesizing enzyme at the synapse. Neuron 32, 79-88.   DOI
156 West, M. A., Bright, N. A. and Robinson, M. S. (1997) The role of ADP-ribosylation factor and phospholipase D in adaptor recruitment. J. Cell Biol. 138, 1239-1254.   DOI
157 Koch, T., Brandenburg, L. O., Schulz, S., Liang, Y., Klein, J. and Hollt, V. (2003) ADP-ribosylation factor-dependent phospholipase $D_2$ activation is required for agonist-induced mu-opioid receptor endocytosis. J. Biol. Chem. 278, 9979-9985.   DOI
158 Kim, J. Y., Soede, R. D., Schaap, P., Valkema, R., Borleis, J. A., Van Haastert, P. J., Devreotes, P. N. and Hereld, D. (1997) Phosphorylation of chemoattractant receptors is not essential for chemotaxis or termination of G-protein-mediated responses. J. Biol. Chem. 272, 27313-27318.   DOI
159 Kim, K. M., Pae, H. O., Zheng, M., Park, R., Kim, Y. M., Chung, H. T. (2007) Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress. Circ. Res. 101, 919-927.   DOI
160 Kim, K. M., Valenzano, K. J., Robinson, S. R., Yao, W. D., Barak, L. S. and Caron, M. G. (2001) Differential regulation of the dopamine D2 and D3 receptors by G protein-coupled receptor kinases and ${\beta}$-arrestins. J. Biol. Chem. 276, 37409-37414.   DOI
161 Koch, W. J., Hawes, B. E., Inglese, J., Luttrell, L. M. and Lefkowitz, R. J. (1994) Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates $G{\beta}{\gamma}$-mediated signaling. J. Biol. Chem. 269, 6193-6197.
162 Kohno, T., Wada, A. and Igarashi, Y. (2002) N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization. FASEB J. 16, 983-992.   DOI
163 Kosugi, S. and Mori, T. (1996) Cysteine-699, a possible palmitoylation site of the thyrotropin receptor, is not crucial for cAMP or phosphoinositide signaling but is necessary for full surface expression. Biochem. Biophys. Res. Commun. 221, 636-640.   DOI
164 Hawtin, S. R., Tobin, A. B., Patel, S. and Wheatley, M. (2001) Palmitoylation of the vasopressin V1a receptor reveals different conformational requirements for signaling, agonist-induced receptor phosphorylation, and sequestration. J. Biol. Chem. 276, 38139-38146.
165 Luttrell, L. M., Daaka, Y., Della Rocca, G. J. and Lefkowitz, R. J. (1997) G protein-coupled receptors mediate two functionally distinct pathways of tyrosine phosphorylation in rat 1a fibroblasts. Shc phosphorylation and receptor endocytosis correlate with activation of Erk kinases. J. Biol. Chem. 272, 31648-31656.   DOI
166 Groarke, D. A., Drmota, T., Bahia, D. S., Evans, N. A., Wilson, S. and Milligan, G. (2001) Analysis of the C-terminal tail of the rat thyrotropin-releasing hormone receptor-1 in interactions and cointernalization with beta-arrestin 1-green fluorescent protein. Mol. Pharmacol. 59, 375-385.   DOI
167 Guo, S., Zhang, X., Zheng, M., Zhang, X., Min, C., Wang, Z., Cheon, S. H., Oak, M. H., Nah, S. Y. and Kim, K. M. (2015) Selectivity of commonly used inhibitors of clathrin-mediated and caveolae-dependent endocytosis of G protein-coupled receptors. Biochim. Biophys. Acta 1848, 2101-2010.   DOI
168 Hanley, N. R. and Hensler, J. G. (2002) Mechanisms of ligand-induced desensitization of the 5-hydroxytryptamine(2A) receptor. J. Pharmacol. Exp. Ther. 300, 468-477.   DOI
169 Hansen, S. H., Sandvig, K. and van Deurs, B. (1993) Clathrin and HA2 adaptors: effects of potassium depletion, hypertonic medium, and cytosol acidification. J. Cell Biol. 121, 61-72.   DOI
170 Hayashi, T., Thomas, G. M. and Huganir, R. L. (2009) Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking. Neuron 64, 213-226.   DOI
171 Henley, J. R., Krueger, E. W., Oswald, B. J. and McNiven, M. A. (1998) Dynamin-mediated internalization of caveolae. J. Cell Biol. 141, 85-99.   DOI
172 Hicke, L. and Riezman, H. (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84, 277-287.   DOI
173 Yu, S. S., Lefkowitz, R. J. and Hausdorff, W. P. (1993) ${\beta}$-adrenergic receptor sequestration. A potential mechanism of receptor resensitization. J. Biol. Chem. 268, 337-341.
174 Williams, A. M. and Enns, C. A. (1993) A region of the C-terminal portion of the human transferrin receptor contains an asparaginelinked glycosylation site critical for receptor structure and function. J. Biol. Chem. 268, 12780-12786.
175 Winstel, R., Freund, S., Krasel, C., Hoppe, E. and Lohse, M. J. (1996) Protein kinase cross-talk: membrane targeting of the ${\beta}$-adrenergic receptor kinase by protein kinase C. Proc. Natl. Acad. Sci. U.S.A. 93, 2105-2109.   DOI
176 Wolfe, B. L. and Trejo, J. (2007) Clathrin-dependent mechanisms of G protein-coupled receptor endocytosis. Traffic 8, 462-470.   DOI
177 Yun, H. J., Kim, H., Ga, I., Oh, H., Ho, D. H., Kim, J., Seo, H., Son, I. and Seol, W. (2015) An early endosome regulator, Rab5b, is an LRRK2 kinase substrate. J. Biochem. 157, 485-495.   DOI
178 Zhang, X., Choi, B. G. and Kim, K. M. (2016a) Roles of dopamine $D_2$ receptor subregions in interactions with ${\beta}$-Arrestin2. Biomol. Ther. (Seoul) 24, 517-522.   DOI
179 Zoncu, R., Perera, R. M., Sebastian, R., Nakatsu, F., Chen, H., Balla, T., Ayala, G., Toomre, D. and De Camilli, P. V. (2007) Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc. Natl. Acad. Sci. U.S.A. 104, 3793-3798.   DOI
180 Zheng, M., Zhang, X., Guo, S., Zhang, X., Min, C., Cheon, S. H., Oak, M. H., Kim, Y. R. and Kim, K. M. (2016) Agonist-induced changes in RalA activities allows the prediction of the endocytosis of G protein-coupled receptors. Biochim. Biophys. Acta 1863, 77-90.   DOI
181 Tanowitz, M. and Von Zastrow, M. (2002) Ubiquitination-independent trafficking of G protein-coupled receptors to lysosomes. J. Biol. Chem. 277, 50219-50222.   DOI
182 Dores, M. R., Chen, B., Lin, H., Soh, U. J., Paing, M. M., Montagne, W. A., Meerloo, T. and Trejo, J. (2012) ALIX binds a $YPX_3L$ motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J. Cell Biol. 197, 407-419.   DOI
183 Holtmann, M. H., Roettger, B. F., Pinon, D. I. and Miller, L. J. (1996) Role of receptor phosphorylation in desensitization and internalization of the secretin receptor. J. Biol. Chem. 271, 23566-23571.   DOI
184 Strasser, R. H., Sibley, D. R. and Lefkowitz, R. J. (1986) A novel catecholamine-activated adenosine cyclic 3',5'-phosphate independent pathway for ${\beta}$-adrenergic receptor phosphorylation in wild-type and mutant S49 lymphoma cells: mechanism of homologous desensitization of adenylate cyclase. Biochemistry 25, 1371-1377.   DOI
185 Subtil, A., Gaidarov, I., Kobylarz, K., Lampson, M. A., Keen, J. H. and McGraw, T. E. (1999) Acute cholesterol depletion inhibits clathrincoated pit budding. Proc. Natl. Acad. Sci. U.S.A. 96, 6775-6780.   DOI
186 Takai, Y., Sasaki, T. and Matozaki, T. (2001) Small GTP-binding proteins. Physiol. Rev. 81, 153-208.   DOI
187 Teis, D., Wunderlich, W. and Huber, L. A. (2002) Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction. Dev. Cell 3, 803-814.   DOI
188 Thompson, D. and Whistler, J. L. (2011) Dopamine D(3) receptors are down-regulated following heterologous endocytosis by a specific interaction with G protein-coupled receptor-associated sorting protein-1. J. Biol. Chem. 286, 1598-1608.   DOI
189 Tran, T. M., Friedman, J., Qunaibi, E., Baameur, F., Moore, R. H. and Clark, R. B. (2004) Characterization of agonist stimulation of cAMP-dependent protein kinase and G protein-coupled receptor kinase phosphorylation of the ${\beta}2$-adrenergic receptor using phosphoserine-specific antibodies. Mol. Pharmacol. 65, 196-206.   DOI
190 Dores, M. R., Grimsey, N. J., Mendez, F. and Trejo, J. (2016) ALIX Regulates the Ubiquitin-Independent Lysosomal Sorting of the P2Y1 Purinergic Receptor via a $YPX_3L$ Motif. PLoS ONE 11, e0157587.   DOI
191 Dutta, D., Williamson, C. D., Cole, N. B. and Donaldson, J. G. (2012) Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS ONE 7, e45799.   DOI
192 D'Souza-Schorey, C., Li, G., Colombo, M. I. and Stahl, P. D. (1995) A regulatory role for ARF6 in receptor-mediated endocytosis. Science 267, 1175-1178.   DOI
193 Eason, M. G., Jacinto, M. T., Theiss, C. T. and Liggett, S. B. (1994) The palmitoylated cysteine of the cytoplasmic tail of ${\alpha}2A$-adrenergic receptors confers subtype-specific agonist-promoted downregulation. Proc. Natl. Acad. Sci. U.S.A. 91, 11178-11182.   DOI
194 Edgerton, M. D., Chabert, C., Chollet, A. and Arkinstall, S. (1994) Palmitoylation but not the extreme amino-terminus of Gq ${\alpha}$ is required for coupling to the NK2 receptor. FEBS Lett. 354, 195-199.   DOI
195 Feig, L. A., Urano, T. and Cantor, S. (1996) Evidence for a Ras/Ral signaling cascade. Trends Biochem. Sci. 21, 438-441.   DOI
196 Ferguson, S. S. (2007) Phosphorylation-independent attenuation of GPCR signalling. Trends Pharmacol. Sci. 28, 173-179.   DOI
197 Ferguson, S. S., Downey, W. E., 3rd, Colapietro, A. M., Barak, L. S., Menard, L. and Caron, M. G. (1996) Role of ${\beta}$-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 271, 363-366.   DOI
198 Ross, E. M. (1995) Protein modification. Palmitoylation in G-protein signaling pathways. Curr. Biol. 5, 107-109.   DOI
199 Cho, D. I., Beom, S., Van Tol, H. H., Caron, M. G. and Kim, K. M. (2006) Characterization of the desensitization properties of five dopamine receptor subtypes and alternatively spliced variants of dopamine $D_2$ and $D_4$ receptors. Biochem. Biophys. Res. Commun. 350, 634-640.   DOI
200 Traub, L. M., Ostrom, J. A. and Kornfeld, S. (1993) Biochemical dissection of AP-1 recruitment onto Golgi membranes. J. Cell Biol. 123, 561-573.   DOI
201 Chow, J. C., Condorelli, G. and Smith, R. J. (1998) Insulin-like growth factor-I receptor internalization regulates signaling via the Shc/mitogen-activated protein kinase pathway, but not the insulin receptor substrate-1 pathway. J. Biol. Chem. 273, 4672-4680.   DOI
202 Claing, A., Chen, W., Miller, W. E., Vitale, N., Moss, J., Premont, R. T. and Lefkowitz, R. J. (2001) ${\beta}$-Arrestin-mediated ADP-ribosylation factor 6 activation and ${\beta}$ 2-adrenergic receptor endocytosis. J. Biol. Chem. 276, 42509-42513.   DOI
203 Claing, A., Laporte, S. A., Caron, M. G. and Lefkowitz, R. J. (2002) Endocytosis of G protein-coupled receptors: roles of G proteincoupled receptor kinases and ${\beta}$-arrestin proteins. Prog. Neurobiol. 66, 61-79.   DOI
204 Clark, R. B., Kunkel, M. W., Friedman, J., Goka, T. J. and Johnson, J. A. (1988) Activation of cAMP-dependent protein kinase is required for heterologous desensitization of adenylyl cyclase in S49 wildtype lymphoma cells. Proc. Natl. Acad. Sci. U.S.A. 85, 1442-1446.   DOI
205 Conaway, R. C., Brower, C. S. and Conaway, J. W. (2002) Emerging roles of ubiquitin in transcription regulation. Science 296, 1254-1258.   DOI
206 Cong, M., Perry, S. J., Lin, F. T., Fraser, I. D., Hu, L. A., Chen, W., Pitcher, J. A., Scott, J. D. and Lefkowitz, R. J. (2001) Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. J. Biol. Chem. 276, 15192-15199.   DOI
207 Schmid, S. L. (1997) Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu. Rev. Biochem. 66, 511-548.   DOI
208 Roth, B. L., Willins, D. L. and Kroeze, W. K. (1998) G protein-coupled receptor (GPCR) trafficking in the central nervous system: relevance for drugs of abuse. Drug Alcohol Depend. 51, 73-85.   DOI
209 Rothberg, K. G., Heuser, J. E., Donzell, W. C., Ying, Y. S., Glenney, J. R. and Anderson, R. G. (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68, 673-682.   DOI
210 Sandvig, K., Olsnes, S., Petersen, O. W. and van Deurs, B. (1987) Acidification of the cytosol inhibits endocytosis from coated pits. J. Cell Biol. 105, 679-689.   DOI
211 Schmidlin, F., Dery, O., DeFea, K. O., Slice, L., Patierno, S., Sternini, C., Grady, E. F. and Bunnett, N. W. (2001) Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1 receptor. J. Biol. Chem. 276, 25427-25437.   DOI
212 Seachrist, J. L., Anborgh, P. H. and Ferguson, S. S. (2000) ${\beta}2$-adrenergic receptor internalization, endosomal sorting, and plasma membrane recycling are regulated by rab GTPases. J. Biol. Chem. 275, 27221-27228.
213 Shapiro, M. J., Weiss, E. J., Faruqi, T. R. and Coughlin, S. R. (2000) Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J. Biol. Chem. 275, 25216-25221.   DOI
214 Shen, Y., Xu, L. and Foster, D. A. (2001) Role for phospholipase D in receptor-mediated endocytosis. Mol. Cell. Biol. 21, 595-602.   DOI
215 Blanpain, C., Wittamer, V., Vanderwinden, J. M., Boom, A., Renneboog, B., Lee, B., Le Poul, E., El Asmar, L., Govaerts, C., Vassart, G., Doms, R. W. and Parmentier, M. (2001) Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J. Biol. Chem. 276, 23795-23804.   DOI
216 Bhattacharya, M., Babwah, A. V., Godin, C., Anborgh, P. H., Dale, L. B., Poulter, M. O. and Ferguson, S. S. (2004b) Ral and phospholipase $D_2$-dependent pathway for constitutive metabotropic glutamate receptor endocytosis. J. Neurosci. 24, 8752-8761.   DOI
217 Bhattacharya, M., Babwah, A. V. and Ferguson, S. S. (2004a) Small GTP-binding protein-coupled receptors. Biochem. Soc. Trans. 32, 1040-1044.   DOI
218 Bizzozero, O. A. (1997) The mechanism and functional roles of protein palmitoylation in the nervous system. Neuropediatrics 28, 23-26.   DOI
219 Boer, U., Neuschafer-Rube, F., Moller, U. and Puschel, G. P. (2000) Requirement of N-glycosylation of the prostaglandin E2 receptor $EP3{\beta}$ for correct sorting to the plasma membrane but not for correct folding. Biochem. J. 350 Pt 3, 839-847.   DOI
220 Boname, J. M., Thomas, M., Stagg, H. R., Xu, P., Peng, J. and Lehner, P. J. (2010) Efficient internalization of MHC I requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains. Traffic 11, 210-220.   DOI
221 Pierce, K. L., Maudsley, S., Daaka, Y., Luttrell, L. M. and Lefkowitz, R. J. (2000) Role of endocytosis in the activation of the extracellular signal-regulated kinase cascade by sequestering and nonsequestering G protein-coupled receptors. Proc. Natl. Acad. Sci. U.S.A. 97, 1489-1494.   DOI
222 Perry, S. J., Baillie, G. S., Kohout, T. A., McPhee, I., Magiera, M. M., Ang, K. L., Miller, W. E., McLean, A. J., Conti, M., Houslay, M. D. and Lefkowitz, R. J. (2002) Targeting of cyclic AMP degradation to ${\beta}$ 2-adrenergic receptors by ${\beta}$-arrestins. Science 298, 834-836.   DOI
223 Pfeffer, S. R. (1994) Rab GTPases: master regulators of membrane trafficking. Curr. Opin. Cell Biol. 6, 522-526.   DOI
224 Pickart, C. M. (2001) Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503-533.   DOI
225 Pippig, S., Andexinger, S. and Lohse, M. J. (1995) Sequestration and recycling of ${\beta}2$-adrenergic receptors permit receptor resensitization. Mol. Pharmacol. 47, 666-676.
226 Pitcher, J. A., Freedman, N. J. and Lefkowitz, R. J. (1998) G proteincoupled receptor kinases. Annu. Rev. Biochem. 67, 653-692.   DOI
227 Poggi, M., Kara, I., Brunel, J. M., Landrier, J. F., Govers, R., Bonardo, B., Fluhrer, R., Haass, C., Alessi, M. C. and Peiretti, F. (2013) Palmitoylation of TNF ${\alpha}$ is involved in the regulation of TNF receptor 1 signalling. Biochim. Biophys. Acta 1833, 602-612.   DOI
228 Pollok-Kopp, B., Huttenrauch, F., Rethorn, S. and Oppermann, M. (2007) Dynamics of protein kinase C-mediated phosphorylation of the complement C5a receptor on serine 334. J. Biol. Chem. 282, 4345-4353.   DOI